scholarly journals TAM Receptors in the Pathophysiology of Liver Disease

Livers ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 15-29
Author(s):  
Emilio Flint ◽  
Evangelos Triantafyllou ◽  
Christine Bernsmeier
Keyword(s):  
Liver Disease ◽  
Acute Liver Injury ◽  
Current Knowledge ◽  
Innate Immune ◽  
Tyrosine Kinase Receptors ◽  
Toll Like Receptor ◽  
Tam Receptors ◽  
Receptor Inhibition ◽  
Receptor Biology ◽  
Parenchymal Cells

TAM receptors (Tyro3, Axl and MerTK) are a family of tyrosine kinase receptors that are expressed in a variety of cell populations, including liver parenchymal and non-parenchymal cells. These receptors are vital for immune homeostasis, as they regulate the innate immune response by suppressing inflammation via toll-like receptor inhibition and by promoting tissue resolution through efferocytosis. However, there is increasing evidence indicating that aberrant TAM receptor signaling may play a role in pathophysiological processes in the context of liver disease. This review will explore the roles of TAM receptors and their ligands in liver homeostasis as well as a variety of disease settings, including acute liver injury, steatosis, fibrosis, cirrhosis-associated immune dysfunction and hepatocellular carcinoma. A better understanding of our current knowledge of TAM receptors in liver disease may identify new opportunities for disease monitoring as well as novel therapeutic targets. Nonetheless, this review also aims to highlight areas where further research on TAM receptor biology in liver disease is required.

scholarly journals Targeting TLR2 for Vaccine Development

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Afonso P. Basto ◽  
Alexandre Leitão
Keyword(s):  
Immune Responses ◽  
Animal Species ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Humoral Immune ◽  
Immunization Strategies ◽  
Contradictory Data ◽  
Effective Immunization

Novel and more effective immunization strategies against many animal diseases may profit from the current knowledge on the modulation of specific immunity through stimulation of innate immune receptors. Toll-like receptor (TLR)2-targeting formulations, such as synthetic lipopeptides and antigens expressed in fusion with lipoproteins, have been shown to have built-in adjuvant properties and to be effective at inducing cellular and humoral immune mechanisms in different animal species. However, contradictory data has arisen concerning the profile of the immune response elicited. The benefits of targeting TLR2 for vaccine development are thus still debatable and more studies are needed to rationally explore its characteristics. Here, we resume the main features of TLR2 and TLR2-induced immune responses, focusing on what has been reported for veterinary animals.

Attenuation of toll-like receptor 2-mediated innate immune response in patients with alcoholic chronic liver disease

2010 ◽  
Vol 30 (7) ◽  
pp. 1003-1011 ◽  
Author(s):  
Pedro Pimentel-Nunes ◽  
Roberto Roncon-Albuquerque ◽  
Nádia Gonçalves ◽  
Cátia Fernandes-Cerqueira ◽  
Hélder Cardoso ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Chronic Liver ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Toll-Like Receptors in the Pathogenesis of Alcoholic Liver Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Jan Petrasek ◽  
Pranoti Mandrekar ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Intracellular Signaling ◽  
Cytokine Production ◽  
Hepatocellular Cancer ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Toll Like Receptors ◽  
Intracellular Signaling Pathways ◽  
Parenchymal Cells

In the multifactorial pathophysiology of alcoholic liver disease (ALD), inflammatory cascade activation plays a central role. Recent studies demonstrated that Toll-like Receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD. In this paper, we discuss the importance of gut-derived endotoxin and its recognition by TLR4. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of reactive oxygen radicals is evaluated. The contribution of TLR signaling to induction of liver fibrosis and hepatocellular cancer is reviewed in the context of alcohol-induced liver disease.

scholarly journals Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas M. Vallance ◽  
Marie-Theres Zeuner ◽  
Harry F. Williams ◽  
Darius Widera ◽  
Sakthivel Vaiyapuri
Keyword(s):  
Platelet Function ◽  
Current Knowledge ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Toll Like Receptor ◽  
Platelet Activity ◽  
Toll Like Receptor 4 ◽  
Open Questions ◽  
Activation Of Transcription ◽  
Wide Range

Platelets are anucleated blood cells that participate in a wide range of physiological and pathological functions. Their major role is mediating haemostasis and thrombosis. In addition to these classic functions, platelets have emerged as important players in the innate immune system. In particular, they interact with leukocytes, secrete pro- and anti-inflammatory factors, and express a wide range of inflammatory receptors including Toll-like receptors (TLRs), for example, Toll-like receptor 4 (TLR4). TLR4, which is the most extensively studied TLR in nucleated cells, recognises lipopolysaccharides (LPS) that are compounds of the outer surface of Gram-negative bacteria. Unlike other TLRs, TLR4 is able to signal through both the MyD88-dependent and MyD88-independent signalling pathways. Notably, despite both pathways culminating in the activation of transcription factors, TLR4 has a prominent functional impact on platelet activity, haemostasis, and thrombosis. In this review, we summarise the current knowledge on TLR4 signalling in platelets, critically discuss its impact on platelet function, and highlight the open questions in this area.

Cardiovascular Risk in Children with Nonalcoholic Fatty Liver Disease (NAFLD)

2020 ◽  
Vol 16 ◽  
Author(s):  
Anna Bobrus- Chociej ◽  
Natalia Wasilewska ◽  
Marta Flisiak- Jackiewicz ◽  
Dariusz Lebensztejn
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Scientific Evidence ◽  
Multisystem Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome

: Nonalcoholic fatty liver disease (NAFLD) is a main cause of chronic liver disease in children. With the global obesity epidemic, the prevalence of NAFLD is increasing both in industrialized and developing countries. NAFLD is a multisystem disorder and a hepatic manifestation of the metabolic syndrome. Growing scientific evidence suggests that NAFLD is an independent risk factor for cardiovascular disease. This paper briefly describes the current knowledge concerning the association between NAFLD and cardiac dysfunction in children.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

scholarly journals Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 95
Author(s):  
Daisuke Tokuhara ◽  
Norikatsu Hikita
Keyword(s):  
Cord Blood ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Current System ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Adult Humans ◽  
Neonates And Infants ◽  
Induced Immunity ◽  
Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

Sign in / Sign up

Export Citation Format

Share Document